Fine-tuning levels of filamins a and b as a specific mechanism sustaining Th2 lymphocyte functions.

Autor: Maire K; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Chamy L; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Ghazali S; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Carratala-Lasserre M; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Zahm M; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Bouisset C; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Métais A; Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France., Combes-Soia L; Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France., de la Fuente-Vizuete L; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Trad H; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Chaubet A; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Savignac M; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Gonzalez de Peredo A; Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France., Subramaniam A; Sanofi Immunology and Inflammation Research Therapeutic Area, Cambridge, MA, USA., Joffre O; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France., Lutz PG; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France. Pierre.Lutz@inserm.fr., Lamsoul I; Infinity, University of Toulouse, CNRS, Inserm, UPS, Toulouse, France. Isabelle.Lamsoul@inserm.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Dec 05; Vol. 15 (1), pp. 10574. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1038/s41467-024-53768-3
Abstrakt: Augmenting the portfolio of therapeutics for type 2-driven diseases is crucial to address unmet clinical needs and to design personalized treatment schemes. An attractive therapy for such diseases would consist in targeting the recruitment of T helper 2 (Th2) lymphocytes to inflammatory sites. Herein, we show the degradation of filamins (FLN) a and b by the ASB2α E3 ubiquitin ligase as a mechanism sustaining Th2 lymphocyte functions. Low levels of FLNa and FLNb confer an elongated shape to Th2 lymphocytes associated with efficient α V β 3 integrin-dependent cell migration. Genes encoding the α V β 3 integrin and ASB2α belong to the core of Th2-specific genes. Using genetically modified mice, we find that increasing the levels of FLNa and FLNb in Th2 lymphocytes reduces airway inflammation through diminished Th2 lymphocyte recruitment in inflamed lungs. Collectively, our results highlight ASB2α and its substrates FLNa and FLNb to alter Th2 lymphocyte-mediated responses.
Competing Interests: Competing interests: A.S. is an employee of Sanofi. The remaining authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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